The management of endoscopic retrograde cholangio- pancreatography-related infections risk: results of an italian survey at regional level.

Background and aim: Among the Endoscopic retrograde cholangiopancreatography (ERCP) adverse events, an increasingly arising problem is the transmission of Multi Drug Resistant (MDR) Bacteria through duodenoscopes. The aim of this survey was to evaluate the current clinical practice of management of ERCP associated infections in Emilia-Romagna, Italy. Methods: An online survey was developed including 12 questions on management of ERCP associated infections risk. The survey was proposed to all 12 endoscopy centers in Emilia Romagna that perform at least > 200 ERCPs per year. Results: 11 centers completed the survey (92%). Among all risk factors of ERCP infections, hospitalization in intensive care units, immunosuppressant therapies, and previous MDR infections have achieved a 80 % minimum of concurrence by our respondents. The majority of them did not have a formalized document in their hospital describing categories and risk factors helpful in the detection of patients undergoing ERCP with an high-level infective risk (9/11, 82%). Most centers (8/11, 72%) do not perform screening in patients at risk of ERCP infections. Post procedural monitoring is performed by 6 of 11 centers (55%). Conclusion: Our survey showed that, at least at regional level, there is a lack of procedures and protocols related to the management of patients at risk of ERCP infections.

Cost Evaluation of Irinotecan-Related Toxicities Associated With the UGT1A1*28 Patient Genotype.

The adoption of a preemptive UGT1A1*28 genotyping to increase irinotecan safety in clinical practice is still limited. This is the first actual study of costs associated with the management of irinotecan-related toxicities, and their association with UGT1A1*28 genotype. A retrospective analysis of the cost of toxicity management was conducted on 243 metastatic colorectal cancer patients enrolled in a clinical trial and treated with standard of care FOLFIRI (5-fluorouracil combined with irinotecan). The mean predicted cost per patient was higher for *28/*28 (€4,886), vs. *1/*1 (€812), (regression coefficient 1.79, 95% confidence interval (CI) = 1.31-2.28; P < 0.001) and for *1/*28 (€1,119) vs. *1/*1 (regression coefficient 0.32, 95% CI = 0.04-0.60; P = 0.024). This is consistent with a different grade 4 toxicity profile among the three genotypes, and a higher frequency of costly interventions like hospitalization among patients with the *28 allele. A differential toxicity management cost by *28 genotype is herein demonstrated, representing a first step towards the demonstration of the test clinical utility.

Literature overview on artificial liver support in fulminant hepatic failure: a methodological approach.

Artificial liver support is a therapeutic option for subjects with fulminant hepatic failure. Results of these studies suggest a possible favourable effect on this condition. The aim of the present review is to evaluate not the results of the different artificial systems available but the methodology used to achieve these results. A computer and manual search of the literature was performed; 832 pertinent references were retrieved. Seventy-seven were full papers reporting the application of artificial liver support in animals or humans (15 RCTs (3 in humans, 12 in animals), 53 uncontrolled phase I trials, 9 case reports). The results of this review indicate that, although the rationale of artificial liver support as shown by animal studies is acceptable, the widespread use in clinical practice is not justified and a controlled design for the studies on artificial liver support systems is mandatory.

Emotional stability, anxiety, and natural killer activity under examination stress.

This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: a combined in situ hybridization and immunocytochemical analysis.

By means of in situ hybridization and immunocytochemical techniques it has been possible to follow the prenatal development of glucocorticoid receptor (GR) messenger RNA (mRNA) expression and GR immunoreactivity (IR) in the rat brain from embryonic day (E) 15 to 22. A 700-base-pair GR cDNA fragment was used for RNA probe generation. In the immunocytochemical analysis a mouse monoclonal antibody (IgG2a) against the rat liver GR was used in combination with the indirect fluorescence technique or the avidin-biotin immunoperoxidase method. At E15 till E22 a moderate to strong GR mRNA signal was observed within the neuro-epithelium from the medulla oblongata to the telencephalon. A moderate to strong labelling was also present within the paraventricular hypothalamic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus. In these areas a weak to moderate nuclear GR IR developed in nerve cells 1 or 2 days after the appearance of the GR mRNA signal. From E15 the adenohypophysis showed the strongest expression of GR mRNA. At E17 a strong GR IR was especially demonstrated in the nuclei of many pituitary cells, some exhibiting adrenocorticotropin IR. The results open up the possibility that there exist active GR in embryonic life capable of regulating proliferation events within the adenohypophysis and the neuro-epithelia of the brain. This embryonic GR may modulate the development of inter alia neuro-endocrine areas such as the paraventricular and arcuate nuclei and arousal-related areas such as the central 5-hydroxytryptamine and noradrenaline neuronal systems. Provided that this embryonic GR is capable of becoming activated by glucocorticoids in fetal life, it may mediate several neurochemical and behavioural impairments caused by prenatal stress.

Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats.

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.

Molecular cloning of PEC-60 and expression of its mRNA and peptide in the gastrointestinal tract and immune system.

The peptide PEC-60, structurally related to the pancreatic secretory trypsin inhibitor, inhibits glucose-induced insulin secretion. Here we report on the structure of a cDNA clone from pig duodenum encoding PEC-60. The cDNA encodes a 86-amino acid long precursor protein containing a 26-amino acid signal sequence, implying that the mature PEC-60 peptide is secreted from cells. Analysis of porcine duodenum demonstrated a high expression of a 0.6-kilobase long PEC-60 mRNA in this tissue, as well as the presence of strong PEC-60-like immunoreactivity in the cytoplasm of the majority of the goblet cells of the epithelium. High levels of PEC-60 mRNA were also found in the bone marrow and the peripheral blood and moderate levels in the spleen. A strong PEC-60-like immunoreactivity was localized in the monocytes of peripheral blood. Radioimmunoassay revealed high levels of pig PEC-60-like immunoreactivity in pig plasma suggesting that the PEC-60 peptide is efficiently released from cells. These findings imply that the gastrointestinal peptide PEC-60 is formed, stored, and secreted from monocytes present within the bone marrow and in the peripheral blood, indicating a role of the PEC-60 peptide in the immune system in addition to its function as a gastrointestinal peptide.

Siagoside selectively attenuates morphological and functional striatal impairments induced by transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: Transient forebrain ischemia induced in rats by the four-vessel occlusion method is known to produce severe neural damage in the hippocampus and striatum and a behavioral syndrome the major symptom of which is a working memory deficit. Recent evidence suggests that monosialogangliosides can ameliorate postischemic symptoms. Our purpose was to study the effect of siagoside, the inner ester of GM1 ganglioside, on some behavioral and morphological impairments induced by four-vessel occlusion in rats. METHODS: Rats were injected daily with 5 mg/kg i.p. siagoside starting 4 hours after the cerebral ischemia. After 14 days the rats were tested for working memory in a water T maze or scored for apomorphine-induced stereotypy. The rats were killed 21 days after the cerebral ischemia. Histological and computer-assisted morphometric analyses were performed on cresyl violet-stained brain sections, which were graded according to a neuropathologic score, and on sections stained with a monoclonal antiserum against dopamine and cyclic adenosine-3',5'-monophosphate-regulated phosphoprotein, a marker for striatal dopaminoceptive neurons. RESULTS: Siagoside treatment reduced the stereotypy score induced by low doses of apomorphine and the extent of striatal lesions but did not affect the working memory deficit or the extent of hippocampal lesions. CONCLUSION: Daily siagoside treatment after acute cerebral ischemia attenuates some morphological and functional deficits related to striatal damage. These effects can be interpreted as a selective protective action on striatal neural populations or as a modulatory action on neural systems involved in striatal control. These data are consistent with preliminary clinical reports showing that monosialogangliosides enhance motor recovery after acute ischemic stroke.

Strongly glucocorticoid receptor immunoreactive neurons in the neonatal rat brain.

Brain glucocorticoid receptor (GR) immunoreactivity was studied in the neonatal rat. Already at postnatal days 1-3 strongly GR immunoreactive (IR) neurons were found in the arcuate and paraventricular hypothalamic nuclei. Moderately to strongly GR IR neurons were found in the locus coeruleus and raphe nuclei, while only weakly GR IR neurons were present in the CA1 and CA2 areas of the hippocampus. GR IR increases steadily during the postnatal period reaching adult levels at day 16. Thus, GR may play a role in the maturation of these hypothalamic nuclei and the 5-hydroxytryptamine and noradrenaline neurons, and GR may provide a basis for the ability of stress-induced increases of glucocorticoids to influence distinct brain circuits during postnatal development.

Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons.

By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all beta-endorphin (beta-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.

Effects of indole-pyruvic acid on sleep and food intake in the rat.

Indole-pyruvic acid was studied for its short- and long-term effects on electroencephalographic sleep and on food intake in rats implanted with cortical and muscular electrodes. Following a single injection, indole-pyruvic acid (10-50 mg kg-1 i.p.) reduced by 16-23 min (range) the latency of the first slow-wave episode in a dose-related fashion and produced a significant increase in slow-wave sleep time (12-40%) in doses of 10-30 mg kg-1. Rapid eye movement sleep latency and rapid eye movement sleep time were increased (by 23-37 min) and reduced (57-71%) respectively. The effects of indole-pyruvic acid on slow-wave sleep time were still present after 3, 7 and 14 days of chronic administration (10 mg kg-1 day-1), whereas tolerance to the effect of indole-pyruvic acid on rapid eye movement sleep was observed. Daily food consumption was reduced (20-28%) by acute administration of indole-pyruvic acid (15-30 mg kg-1 i.p.), but tolerance developed after 5 days of repeated injections. These findings are in accordance with previous evidence suggesting that indole-pyruvic acid effects may be related to the activation of central serotonin neurons, which are involved in the inhibitory control of sleep and food intake.